An Efficacy Study of Paliperidone for the Prevention of Relapse in Participants With Schizophrenia

NCT01662310 | Completed Phase 3 Results DMC

• 2 other identifiers: CR100427R076477-SCH-3041
• Study Type: interventional
• Target: 201
• Locations: 1 country
• Sites: 14

Brief Summary

The purpose of this study is to evaluate the efficacy, tolerability and safety of paliperidone extended release (ER) tablets (between 3 to 12 milligram (mg), once a day) in the prevention of relapse in schizophrenia participants.

Conditions

Schizophrenia

Keywords

Schizophrenia; Paliperidone; Paliperidone Extended-Release

Outcome Measures

Primary Outcomes (1)

• Double Blind (DB) Phase: Median Time to Relapse

  A relapse is defined as any one of the following: 1. involuntary or voluntary psychiatric hospitalization 2. deliberate self-injury or violent behavior; 3. Suicidal or homicidal ideation and clinically significant aggressive behavior; 4. 25 percent (%) increase in Positive and Negative Syndrome Scale (PANSS) total score for 2 consecutive assessments for participants whose score was greater than 40 at randomization, or a 10-point increase for participants who scored less than or equal to (≤) 40 at randomization; 5. increase for 2 consecutive assessments in PANSS items (delusions, conceptual disorganization, hallucinatory behavior, suspiciousness, hostility or uncooperativeness) to greater than or equal to (≥) 5 for participants who scored ≤3 at randomization, or to ≥6 for participants with initial score of 4. Independent Data Monitoring Committee performed ongoing safety monitoring during double-blind treatment and conducted the interim analysis after 61 relapse events had taken place.

  DB Baseline (Day 1 of Week 15) up to interim analysis data cut-off (24 August 2012) (Approximately 1 year)

Secondary Outcomes (14)

• Run-In and Stabilization Phase: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 14

  Baseline and Week 14

• Double Blind (DB) Phase: Change From DB Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at DB Endpoint

  DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year])

• Run-In and Stabilization Phase: Number of Participants Assessed With Categorical Scores Based on Clinical Global Impression-Severity Scale (CGI-S)

  Baseline and Week 14

• Double Blind (DB) Phase: Change From DB Baseline in Clinical Global Impression-Severity Scale (CGI-S) Total Score at DB Endpoint

  DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year])

• Run-In and Stabilization Phase: Change From Baseline in Personal and Social Performance (PSP) Scale Total Score at Week 14

  Baseline and Week 14

Study Arms (3)

Paliperidone: Run-in or Stabilization phase

EXPERIMENTAL

Paliperidone extended-release (ER) oral tablet will be administered at a starting dose of 3 milligram (mg) once daily for 8 weeks. Dose will be increased from milligram per day (3 mg/day) after 5 days based on Investigator's discretion, up to maximum of 12 mg/day.

Drug: Paliperidone

Paliperidone: Double blind (DB) phase

EXPERIMENTAL

Participants who transitioned from run-in or stabilization phase received 3 to 12 mg fixed dose of paliperidone ER oral tablet once daily during DB phase of the study. Participants who will experience a relapse event during the DB phase or who will remain relapse free for the entire duration of the DB phase and participants, who will be enrolled at the time the study termination will enter in open label extension phase, wherein paliperidone ER oral tablet will be administered once daily as 3 to 12 mg.

Drug: Paliperidone

Placebo: DB phase

ACTIVE COMPARATOR

Participants who transitioned from run-in or stabilization phase received matching placebo to paliperidone ER once daily during DB phase of the study. Participants who will experience a relapse event during the DB phase or who will remain relapse free for the entire duration of the DB phase and participants, who will be enrolled at the time the study termination will enter in open label extension phase, wherein paliperidone ER oral tablet will be administered once daily as 3 to 12 mg.

Drug: Placebo

Interventions

Paliperidone DRUG

Paliperidone extended-release (ER) oral tablet will be administered at a starting dose of 3 milligram (mg) up to 12 mg once daily for 8 weeks in Run-in or Stabilization phase, and 3-12 mg fixed dose oral tablet will be administered in DB phase. Participants who will enter open-label extension phase will receive paliperidone as 3-12 mg per day.

Also known as: R076477

Paliperidone: Double blind (DB) phase; Paliperidone: Run-in or Stabilization phase

Placebo DRUG

Participants who transitioned from run-in or stabilization phase will receive matching placebo to paliperidone ER once daily during DB phase of the study.

Placebo: DB phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a diagnosis of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)
• Have experienced an acute episode, with a Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120 inclusive, at Screening and Baseline
• Women must be postmenopausal (for at least 1 year), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), practicing a highly effective method of birth control, if sexually active
• Men must be using a highly effective method of birth control and must not donate sperm during the study and for 3 months after receiving the last dose of study drug
• Be willing and capable to complete the questionnaires and able to take oral medications independently

You may not qualify if:

• Has drug dependence diagnosis according to DSM-IV (excluding nicotine and caffeine dependence) within 6 months before screening
• Participants with Crohn's disease and hepatic or renal diseases
• Has had relevant history of any significant and/or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular dysfunction), renal, hepatic, endocrine, or immunologic diseases
• Has had history of neuroleptic malignant syndrome (the disorder caused by antipsychotic drugs with symptoms of fever, muscle rigidity and delirium)
• Has had known or suspected Stevens Johnson Syndrome (an immune disease with symptoms of fever, sore throat, ulcers and conjunctivitis) after exposure to phenytoin, carbamazepine, barbiturates, or lamotrigine
• Had been treated with clozapine for treatment refractory or treatment resistant schizophrenia
• Has significant risk of suicide or homicidal behavior, or significant risk of deliberate self harm or harm to others
• Has taken isocarboxazid, phenelzine, selegiline and tranylcypromine within 4 weeks before screening
• Has received electroconvulsive therapy within 60 days before screening

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (14)

Unknown Facility

Baoding, China

Location

Unknown Facility

Beijing, China

Location

Unknown Facility

Changsha, China

Location

Unknown Facility

Chengdu, China

Location

Unknown Facility

Guangzhou, China

Location

Unknown Facility

Harbin, China

Location

Unknown Facility

Kunming, China

Location

Unknown Facility

Nanjing, China

Location

Unknown Facility

Shanghai, China

Location

Unknown Facility

Taiyuan, China

Location

Unknown Facility

Tianjin, China

Location

Unknown Facility

Wuhan, China

Location

Unknown Facility

Xi'an, China

Location

Unknown Facility

Xinxiang, China

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Paliperidone Palmitate

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Limitations and Caveats

Independent Data Monitoring Committee (IDMC) conducted an interim analysis after 61st relapse in double-blind (DB) phase and DB phase completed on 09-Nov-2012 based on positive results of interim analysis.

Results Point of Contact

• Title: Senior Director Clinical Leader
• Organization: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

ClinicalTrialDisclosure@its.jnj.com

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2012
• First Posted: August 10, 2012
• Study Start: June 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: September 29, 2014
• Results First Posted: June 6, 2014

Record last verified: 2014-09

Locations

CN (14)